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Study Summary
No. ACOSOGZ1031:.......Breast......Gildy V. Babiera......Surgical Oncology
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Study Summary Title
Study Summary
Number:
ACOSOGZ1031
Study Title:A Randomized Phase III Trial Comparing 16 to 18 Weeks of Neoadjuvant Exemestane (25 mg daily), Letrozole (2.5 mg), or Anastrozole (1 mg) in Postmenopausal Women with Clinical Stage II and III Estrogen Receptor Positive Breast Cancer
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Physician New Patient Referral
Name:Gildy V. BabieraPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Surgical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-6940
Contact us about clinical trials
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General Information
Disease Group:BreastSupported By:ACOSOG
Phase of Study:Phase IIIReturn
Visit:
Treatment
Agents:
Anastrazole
Exemestane
Letrozole
Home Care:
Treatment Loc:Both at MDACC & and Other Sites
Estimated
Length of Stay
in Houston:
Description/
Intervention:
The goal of this screening biopsy is to show if you have a type of breast
cancer that is affected by the levels of hormones in your body. If you have
this type of breast cancer, you may qualify for participation in the
ACOSOGZ1031 main study. If you qualify, you will be given the main study
consent to sign, which will provide more information about the study. This
consent form is intended only as a screening consent form for tissue
collection.
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Study Objectives / Outcomes
Primary Objectives
Cohort A: To determine whether anastrozole, exemestane or letrozole administered for 16 to 18 weeks as neoadjuvant endocrine treatment for postmenopausal patients with stage II or stage III ER+ breast cancer should be chosen as the aromatase inhibitor arm of a future study that will compare neoadjuvant aromatase inhibitor treatment with neoadjuvant chemotherapy.

Cohort B (patients enrolled after the 375th patient): To determine whether patients who have a high Ki67 value (>10%) after 2 weeks of neoadjuvant AI treatment experience a higher than expected pathological response rate to neoadjuvant chemotherapy (20%) than would be typically observed for postmenopausal patients with unselected ER rich tumors (estimated to be 5%), indicating that an early assessment of proliferation is a useful approach to the identification of a chemotherapy sensitive subgroup of ER+ tumors.

Secondary Objectives
1. To compare the neoadjuvant treatment regimens relative to the rates of improvement in surgical outcome defined as follows:
  • For T4 a, b, c, tumors: mastectomy with primary skin closure and negative surgical margins
  • For T3 tumors and T2 tumors classified as requiring mastectomy at baseline: breast conserving surgery with negative final margins
  • For T2 tumors classified as potential candidates for breast conservation: wide excision at first attempt

2. To compare and confirm the radiological response rates (mammography by central radiological analysis) between these three neoadjuvant treatment regimens.

3. To compare the relative safety of the neoadjuvant treatment regimens in terms of reported adverse events.

4. To compare the tumor pathologic size between the neoadjuvant treatment regimens and to compare the rates of pathological CR (defined as no invasive cancer in the post-treatment specimen), and to compare down-staging to Stage I, defined as a finding of 2cm or less invasive cancer in the breast at surgery, with pathologically negative lymph-nodes.

5. To compare the rate of complete cell cycle response between the three treatment regimens (Ki67 staining of 1% or less in the post treatment sample.)

6. To compare the incidence of metastatic lymph node involvement on the three arms of the study in patients who have lymph node dissection at the end of neoadjuvant treatment.

7. To determine the 10-year incidence of local recurrence after neoadjuvant aromatase inhibitor therapy.

8. To collect tumor tissue, serum specimens, and plasma specimens to develop predictive biomarkers that can be used to select tumors for neoadjuvant aromatase inhibitor therapy. (The Preoperative Endocrine Prognostic Index (PEPI) is a robust indicator of relapse free survival).

9. To collect surgical specimens post-AI neoadjuvant therapy to identify markers of de novo resistance to AI therapy.
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Study Status Information
Study Activation / Registration Date:03/24/2006
IRB Review and Approval Date:03/01/2006
Study Type:Therapeutic
Recruitment Status:Closed
Projected Accrual:610
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patient must have an ECOG/Zubrod performance status of less than or equal to 2.

2) Patient must have T2-T4c, any N, M0 breast cancer, by clinical staging. NOTE: Primary tumor must be palpable and measure great than 2 cm by tape, ruler or caliper measurements in at least one dimension.

3) Patient must be postmenopausal, verified by a) bilateral surgical oophorectomy; or b) No spontaneous menses greater than or equal to 1 year; c) No menses for less than 1 year with FSH and estradiol levels in postmenopausal range, according to institutional standards

4) Patient, as documented by the treating physician, is clinically staged as one of the following: a) T4 a-c for whom modified radical mastectomy with negative margins is the goal; b) T2 or T3 for whom conversion from needing mastectomy to breast conservation is the goal; c) T2 for whom lumpectomy at first attempt is the goal

5) Patient has an ER+ tumor with an Allred score of 6, 7 or 8. Note: Patients with greater than 66.6% (two-thirds) of cells staining positive have a minimum Allred score of 6 and are eligible.

6) Patient must have mammogram and ultrasound within 42 days prior to registration.

7) If patient is a cancer survivor, all of the following criteria must be met: a) Patient has undergone potentially curative therapy for all prior malignancies; b) No evidence of any prior malignancies for at least 5 years with no evidence of recurrence (except for successfully treated cervical carcinoma in situ, lobular carcinoma in situ of the breast, contralateral DCIS treated with mastectomy or lumpectomy and radiation, but without tamoxifen treatment,or non-melanoma skin cancer with no evidence of recurrence);

8) Continued from Inclusion # 7: and, c) Patient is deemed by their treating physician to be at low risk for recurrence from prior malignancies

9) This inclusion criteria is only in the M. D. Anderson Abstract and is not in the protocol. It applies to M. D. Anderson patients only: Any patient with T2-T4 tumors, excluding T4d, classified as requiring mastectomy by surgeon at baseline and unlikely to be breast conservation surgery (bcs) candidates after completing protocol, can be considered for enrollment.

10) This inclusion criteria is only in the M. D. Anderson Abstract and is not in the protocol. It applies to M. D. Anderson patients only: Any patient desiring mastectomy prior to enrolling on protocol and desiring mastectomy at completion of protocol can be considered for enrollment.

Exclusion Criteria:1) Inflammatory breast cancer defined as clincally significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema)

2) Prior treatment for invasive breast cancer, including radiation, endocrine therapy, chemotherapy or investigational agent. Patients whose diagnosis was established by incisional biopsy are not eligible.

3) Patient has received hormone replacement therapy of any type, megestrol acetate or raloxifene within one week prior to registration

4) Patient has distant metastasis (M1), excluding isolated ipsilateral supraclavicular node involvement

5) Patient does not agree to undergo mastectomy or lumpectomy after neoadjuvant aromatase inhibitor therapy

6) Patient is enrolled in another neoadjuvant clinical trial for treatment of the existing breast cancer

7) Patients whose tumors are Her 2-neu positive.

8) Cohort B only: Patient has undergone prior sentinel lymph node biopsy.

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Links
Registration Number: NCT00265759
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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